99718-67-9

Usage

Type of Compound

Chemical compound

Target

Potent inhibitor of the receptor tyrosine kinase, vascular endothelial growth factor receptor 2 (VEGFR2)

Potential Therapeutic Effects

Treatment of diseases characterized by abnormal angiogenesis (such as cancer and ocular disorders) and potential neuroprotective effects in conditions such as stroke and neurodegenerative diseases

Need for Further Research

To fully understand its pharmacological properties and potential clinical applications

Upstream product

• 35386-24-4 1-(2-Methoxyphenyl)piperazine 
• 574-98-1 2-(2-bromoethyl)isoindoline-1,3-dione 
• 5464-78-8 1-(2-methoxyphenyl)piperazine hydrochloride 
• 1074-82-4 potassium phtalimide 

Downstream Products

• 188017-73-4 2-(4-(2-methoxyphenyl)piperazin-1-yl)ethanamine hydrochloride 
• 223521-29-7 N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)eth-1-yl)-N-3-(4-(6-fluoroindol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl)prop-1-ylamine 
• 223521-46-8 4-[2-((3'-bromo)propionamido)ethyl]-1-(2-methoxyphenyl)piperazine 
• 223521-25-3 N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)eth-1-yl)-3-(4-(6-chloroindol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl)propanamide 
• 223521-24-2 N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)eth-1-yl)-3-(4-(6-fluoroindol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl)propanamide 
• 1608157-08-9 2-(furan-2-yl)-N⁵-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine 

Relevant academic research and scientific papers

Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands

Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3/sub

Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D4 Receptor Agonists with High Subtype Selectivity

Many subtype-selective dopamine receptor ligands developed for the D2-D4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to Ki(D4.4) = 0.25 nM, D2L/D4.4 = 320, D3/D4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D4 receptor showing significant bias toward G protein activation over β-arrestin recruitment in comparison to quinpirole.

Photochromic Dopamine Receptor Ligands Based on Dithienylethenes and Fulgides

We describe the incorporation of the well-investigated class of photochromic dithienylethenes (DTEs) and fulgides into known dopamine receptor ligands such as 1,4-disubstituted aromatic and hydroxybenzoxazinone piperazines as well as aminoindanes. Subtype

Discovery of naphthalimide conjugates as fluorescent probes for α1-adrenoceptors

α1-Adrenoceptors (α1-ARs), including at least three subtypes, α1A, α1B and α1D, which play essential roles in G protein-coupled receptors (GPCRs), can convey multiple pivotal extracellular signals in varied tissues and organs. In this research, a series of napthalimide-based small-molecule fluorescent probes (1a–1f) for α1-ARs, including two parts, a pharmacophore (quinazoline and phenylpiperazine) for α1-AR recognition and a fluorophore (naphthalimide) for visualization, were designed and synthesized successfully. These compounds display excellent fluorescence property and high affinity to receptors, which were used successfully for in vitro visualization of α1-adrenoceptors.

Binding kinetics of ZM241385 derivatives at the human adenosine A 2A receptor

Classical drug design and development rely mostly on affinity- or potency-driven structure-activity relationships (SAR). Thus far, a given compound's binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure-kinetics relationship (SKR) study in addition to a traditional SAR analysis at the adenosine A2A receptor (A 2AR). The ensemble of 24 A2AR compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino) ethyl)phenol), displayed only minor differences in affinity, although they varied substantially in their dissociation rates from the receptor. We believe that such a combination of SKR and SAR analyses, as we have done with the A 2AR, will have general importance for the superfamily of G protein-coupled receptors, as it can serve as a new strategy to tailor the interaction between ligand and receptor. Above and beyond: Insight into the binding kinetics of ZM241385 derivatives at the human adenosine A2A receptor has provided additional information beyond a traditional structure-activity relationship (SAR) analysis. The strategy, combining a structure-kinetics relationship investigation and SAR, can serve as an important tool for more directed medicinal chemistry efforts in the future.

Synthesis of several MPP derivatives for 99mTc-labelling and evaluated as potential 5-HT1A receptor imaging agents

The (2-methoxyphenyl) piperazine (MPP) was selected as the functional group and conjugated to dithiocarbamate through different spacers. A series of new MPP derivatives (MPPnDTC, n = 2-6) were synthesized and radiolabelled with 99mTc-nitrido core or 99mTc-tricarboxyl core as potential 5-HT1A receptor imaging agents. All the six 99mTc-labelled complexes were lipophilic and neutral. Biodistribution results showed that those radiotracers had moderate initial brain and hippocampus uptake. There have no significant relation was observed between the biological properties of these tracers with the length of its carbon chain. The radioactivity concentrations of hippocampus of 99mTcN-MPP2DTC, 99mTcN-MPP3DTC, 99mTcN-MPP4DTC, 99mTcN-MPP5DTC, 99mTcN-MPP6DTC and 99mTc(CO)3-MPP3DTC at 2 min post-injection time (p.i.) were 0.43, 1.15, 0.99, 1.04, 1.13 and 0.83 %ID/g, respectively.

Synthesis and biological evaluation of oxazole derivatives as T-type calcium channel blockers

T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pain. In this study, as a part of our ongoing efforts to develop potent T-type calcium channel blockers, we designed oxazole derivatives subs

Chemical modifications on 4-arylpiperazine-ethyl carboxamide derivatives differentially modulate affinity for 5-HT1A, D4.2, and α2A receptors: Synthesis and in vitro radioligand binding studies

A series of substituted 4-aryl-piperazine-ethyl heteroarylcarboxamides were prepared and tested in in vitro radioligand binding studies. The presence of a quinoxaline has a favourable impact in terms of serotonin 5-HT1A versus dopamine D4.2 receptor selectivity. Compounds with a 3-CF3 group at the distal phenyl ring are the most effective in terms of affinity and selectivity for 5-HT1A versus D4.2 receptors. A 4-phenyl-1,2,3,6- tetrahydropyridine in place of the corresponding 4-phenyl-piperazine side chain is also favourable not only for the affinity for 5-HT1A and D4.2 receptors but also in some cases for α2A-adrenoceptors.

Synthesis and in vitro binding studies of piperazine-alkyl-naphthamides: Impact of homology and sulphonamide/carboxamide bioisosteric replacement on the affinity for 5-HT1A, α2A, D4.2, D3 and D2L receptors

A series of carboxamide and sulphonamide alkyl(ethyl to hexyl)piperazine analogues were prepared and tested for their affinity to bind to a range of receptors potentially involved in psychiatric disorders. These chemical modifications led us to explore th

Synthesis and biological affinity of new imidazo- and indol-arylpiperazine derivatives: Further validation of a pharmacophore model for α1-adrenoceptor antagonists

In the continuing search for selective α1-adrenoceptor (AR) antagonists, new alkoxyarylpiperazinylalkylpyridazinone derivatives were designed and synthesized. The new compounds were tested for their affinity toward α1-AR, α2-AR and 5-HT1A receptors. The ability of these compounds to inhibit the serotonin transporters (SERT) was also determined. The pharmacological data confirm that increasing the size of the ortho alkoxy substituent on the phenyl ring of the arylpiperazine moiety afforded compounds with enhanced affinity toward the α1-AR. The isopropoxy group, the largest group evaluated, led the best α1-AR affinity profile. In contrast, the compounds which have an amide group within of the o-alkoxy-phenylpiperazine fragment showed low affinity toward the receptors studied. Similar results were obtained when the amide group was present in the linker of the junction between the two major constituents of the molecule.